Grant: Foundation Grant

Normal function of the brain depends on tightly regulated communication between neurons. The neurons communicate with one another through junction sites called synapses via "synaptic transmission". During this process, neurotransmitter molecules are released from presynaptic neurons and bind to receptors on the postsynaptic neurons. Deregulated synaptic transmission is believed to be at the root of many brain diseases such as Alzheimer's disease, Parkinson's disease, schizophrenia, anxiety disorders, epilepsy, and stroke. I believe that by better understanding the mechanisms controlling the efficacy of the synaptic transmission among neurons there is the potential to identify targets and thereby to create better therapeutics for these brain disorders. Theoretically, the strength of synaptic transmission can be regulated by altering either the presynaptic neurotransmitter release or the responsiveness of postsynaptic neurotransmitter receptor. Research in our laboratory has focused on the regulatory mechanisms which determine the responsiveness of postsynaptic ionotropic receptors. Strong evidence accumulated from our work and other labs suggest that both function and number of these receptors may be rapidly altered. These rapid changes may be responsible for the pathogenesis of many brain disorders. Currently, we are proposing experiments to investigate how rapid changes in the function and number of postsynaptic receptors, therefore synaptic transmission strength, is regulated. The main objective of our research is to identify molecular processes underlying the regulation of the efficacy of synaptic transmission. Through these fundamental investigations we aim to identify new therapeutic targets and develop new drugs to treat brain disease. Since inter-neuronal communication is a pivotal component of brain function and the alteration of this process underlies many disorders, our proposed studies can be expected to lead to better treatment for these diseases